Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer

Sponsor
The Netherlands Cancer Institute
Study ID
NCT03026140
Phase
PHASE2
Status
Recruiting
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Conditions

  • Colon Carcinoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Nivolumab — DRUG
    Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
  • Ipilimumab — DRUG
    Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery
  • Celecoxib 200mg — DRUG
    celecoxib will be administered starting day 1 until 1 day before surgery daily (if patient is randomized to group 2 (only applicable for patients with a MSS tumor)
  • BMS-986253 — DRUG
    BMS-986253 2400mg IV will be administered on day 1 and 15 (only applicable for patients with MSS tumors)
  • BMS-986016 — DRUG
    Relatlimab will be administered IV, in cohort 5 240mg on day 1 and day 15, in cohort 6 480mg on day 1 and day 29, in cohort 7 160mg on day 1, day 29 and day 57

Study Details

In this exploratory study, patients with stage 1-3 adenocarcinoma of the colon with no signs of distant metastases will be treated with short-term immunotherapy + novel IO combinations (i.e. anti-IL 8, COX2-inhibitors, anti-LAG3). This treatment will be given during the window period until surgical resection of the tumor. The duration of treatment will be in between approximately 6 and 12 weeks.

Key Dates

Start date
Mar 29, 2017
Status verified
Mar 2026
Primary completion
Mar 1, 2032
Completion
Mar 1, 2032

Study Design

Enrollment
353 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: group 1 - closed
    drug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV)
  • Experimental: group 2 - closed
    drug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV) drug: celecoxib 200 mg daily (oral)
  • Experimental: Anti-IL8 cohort 4 (pMMR/MSS tumors) - closed
    drug: nivolumab 3 mg/kg day 1 and day 15 (IV) drug: BMS-986253 (anti-IL8) 2400mg on day 1 and day 15 (IV)
  • Experimental: Relatlimab cohort 5 (pMMR/MSS tumors)
    drug: nivolumab 240mg IV on day 1 and day 15 drug: relatlimab 240mg IV on day 1 and day 15
  • Experimental: Relatlimab cohort 6 (dMMR/MSI tumors) - closed
    drug: nivolumab 480mg IV on day 1 and day 29 drug: relatlimab 480mg IV on day 1 and day 29
  • Experimental: Cohort 7 - dMMR - 3 cycles neoadjuvant nivolumab + relatlimab
    Patients with dMMR tumors will be treated with 3 cycles of neoadjuvant nivolumab (480mg) + relatlimab (160mg) on day 1, day 29 and day 57 followed by surgery within 12 weeks and not earlier than 10 weeks from enrollment
  • Experimental: Cohort 8 - dMMR - 3 cycles neoadjuvant nivolumab - closed
    Patients with dMMR tumors will be treated with 3 cycles of neoadjuvant nivolumab (480mg) on day 1, day 29 and day 57 followed by surgery within 12 weeks and not earlier than 10 weeks from enrollment.

Primary Outcome Measure

Incidence of adverse events during the treatment and follow-up (safety) [ Time Frame: until 100 days after last patient last study drug treatment ]

Central Contacts

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